HSCT corrects primary immunodeficiency and immune dysregulation in patients with POMP-related auto-inflammatory disease

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dc.contributor.authorMartinez, Caridad
dc.contributor.authorEbstein, Frédéric
dc.contributor.authorNicholas, Sarah K.
dc.contributor.authorGuzman, Marietta De
dc.contributor.authorForbes, Lisa R.
dc.contributor.authorDelmonte, Ottavia M.
dc.contributor.authorBosticardo, Marita
dc.contributor.authorCastagnoli, Riccardo
dc.contributor.authorKrance, Robert
dc.contributor.authorNotarangelo, Luigi D.
dc.contributor.authorKrüger, Elke
dc.contributor.authorOrange, Jordan S.
dc.contributor.authorPoli, Cecilia
dc.date.accessioned2022-04-07T17:51:44Z
dc.date.available2022-04-07T17:51:44Z
dc.date.issued2021
dc.description.abstractInborn errors of immunity that present with concomitant immunodeficiency and auto-inflammation are therapeutically challenging; furthermore, complexity is added when they are caused by mutations in genes that encode for proteins expressed beyond immune cells. The ubiquitin-proteasome system is the main intracellular proteolytic machinery and participates in most cellular processes by degrading ubiquitinated proteins. Mutations in proteasome subunits resulting in proteasome deficiency cause a severe autoinflammatory disease characterized by chronic auto-inflammation neutrophilic dermatosis and fever, collectively referred to as Proteasome Associated Auto-inflammatory Syndromes (PRAAS). POMP is a chaperone for proteasome assembly and AD mutations in POMP cause a form of PRAAS with prominent immunodeficiency referred to as POMP-related auto-inflammation and immune dysregulation (PRAID) manifesting with recurrent, severe and opportunistic infections in addition to inflammatory features that are characteristic for all PRAAS disorders, most importantly early-onset neutrophilic dermatosis. JAK inhibitors partially control the disease in individuals with PRAAS, however life-threatening, recurrent and opportunistic infections in patients with POMP mutations limit immunosuppressive therapies and prompted consideration of hematopoietic stem cell transplant (HSCT). We describe successful HSCT in two patients with POMP deficiency. Despite POMP being ubiquitously expressed, the immunologic and autoinflammatory phenotype were both ameliorated through HSCT which suggests that the clinical and immunological features of PRAID are predominantly derived from a proteasome defect in hematopoietic cells. To our knowledge, these are the first patients with a form of PRAAS cured by HSCT, opening new therapeutic possibilities for these diseases.es
dc.description.versionVersión enviadaes
dc.identifier.citationMartinez C, Ebstein F, Nicholas SK, De Guzman M, Forbes LR, Delmonte OM, Bosticardo M, Castagnoli R, Krance R, Notarangelo LD, Krüger E, Orange JS, Poli MC. HSCT corrects primary immunodeficiency and immune dysregulation in patients with POMP-related autoinflammatory disease. Blood. 2021 Nov 11;138(19):1896-1901. doi: 10.1182/blood.2021011005.es
dc.identifier.urihttps://doi.org/10.1182/blood.2021011005es
dc.identifier.urihttp://hdl.handle.net/11447/5956
dc.language.isoenes
dc.subjectImmunobiology and Immunotherapyes
dc.subjectTransplantationes
dc.titleHSCT corrects primary immunodeficiency and immune dysregulation in patients with POMP-related auto-inflammatory diseasees
dc.typeArticlees
dcterms.sourceBloodes

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